The primary goal of this P01 is to improve the outcomes and lives of patients with thyroid cancer by identifying genetically """"""""at-risk"""""""" individuals allowing for early diagnosis and prediction of tumor behavior, new pathways that influence cancer development and progression, and improving outcomes of patients with metastatic disease by improving existing therapies or validating new treatment targets. Several factors support the importance of applying these efforts to thyroid cancer: (1) Thyroid cancer incidence is rising at the fastest rate of all malignancies in the United States. (2) Thyroid cancer typicall takes an indolent course when patients are diagnosed early, thus with the increasing incidence there is an ever enlarging population of individuals surviving long-term. (3) For patients with more aggressive forms of thyroid cancer, current treatment options need to be improved or replaced with more effective treatments. Over the course of the first cycle of this P01 our group has together worked toward these goals and made key observations with potential to impact on patients with differentiated thyroid cancer (papillary and follicular). The goal for this competing renewal is to extend the work on the most promising findings that have greatest likelihood to be translated into practice or that represent key advances in the field with potential to alter paradigms used in research or clinical practice. Specifically, we will functionally characterize genes that predispose to PTC in families identified in the first cycle of the P01 and apply new technologies to a larger number of informative families to identify more potential genes that predispose to PTC (Project 1), extend the work using a candidate gene approach for FTC and PTC risk that has identified interactions between signaling pathways (Project 2);design approaches to enhance 1-131 therapy using novel mouse imaging techniques developed in the P01 and extend that work to identify other unknown regulators of this process (Project 3);and fully determine the role and potential therapeutic importance of p21 activated kinase (PAK), a newly identified signaling pathway downstream of BRAF, in thyroid cancer in vivo, and determine its role in resistance to RAF inhibitors (Project 4).

Public Health Relevance

Thyroid cancer incidence is rising. Key issues in clinical care relate to defining the risk of developing thyroid cancer, identifying key pathways involve in tumor formation or predisposition, developing methods to improve existing treatments, and defining pathways involved in disease progression to develop new therapies. This P01 addresses these critical areas to improve the outcomes of patients with thyroid cancer.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Research Program Projects (P01)
Project #
5P01CA124570-07
Application #
8657014
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Yassin, Rihab R,
Project Start
2006-12-01
Project End
2018-03-31
Budget Start
2014-04-17
Budget End
2015-03-31
Support Year
7
Fiscal Year
2014
Total Cost
Indirect Cost
Name
Ohio State University
Department
Internal Medicine/Medicine
Type
Schools of Medicine
DUNS #
City
Columbus
State
OH
Country
United States
Zip Code
43210
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Ni, Ying; Seballos, Spencer; Fletcher, Benjamin et al. (2017) Germline compound heterozygous poly-glutamine deletion in USF3 may be involved in predisposition to heritable and sporadic epithelial thyroid carcinoma. Hum Mol Genet 26:243-257
Ashtekar, Amruta; Huk, Danielle; Magner, Alexa et al. (2017) Sdhd ablation promotes thyroid tumorigenesis by inducing a stem-like phenotype. Endocr Relat Cancer 24:579-591

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